Lack of oligophrenin-1 expression has been implicated in non-specific X-linked mental retardation (MRX). Oligophrenin-1 is highly expressed in the brain, and contains a putative Rho GTPase activating protein (GAP) domain. The goal of this study is to determine how a lack of oligophrenin-1 results in a phenotype of mental retardation on a molecular and morphological level, and how its interaction(s) with Rho family GTPases contributes to this phenotype. The specific aims are as follows: 1) To determine which GTPase oligophrenin-1 acts upon in a cellular context using Rhotekin Rho-Binding Domain and PAK3-binding assays to quantitate the amount of activated Rho GTPases in PC12 cells transfected with an oligophrenin-1 expression construct compared to control cells, 2) To determine what effect oligophrenin-1 has on cellular morphology in developing neurons by doing live cell imaging of biolistically-transfected pyramidal cells in hippocampal slices over time using two-photon microscopy, and 3) To determine how a lack of oligophrenin-1 affects dendritic length and spine formation in the above system. Information gained from studies on oligophrenin-1 will correlate basic cellular and molecular biology with the disease phenotype of mental retardation and will provide us with a better understanding of neuronal development and MRX. Ultimately, knowledge of these regulatory pathways may lead to treatment for this common condition.